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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003E\n               \u003Cem\u003EEGFR\u003C\/em\u003E mutations can be analyzed with circulating tumor DNA, with an overall concordance of \u003Cem\u003EEGFR\u003C\/em\u003E mutation status of 89%. The low positive predictive value of 78% was likely due to false-negative tumor samples using less sensitive methodologies such as DNA sequencing or pyrosequencing, and it increased to 93% when highly sensitive methods such as the QIAGEN Therascreen RGQ PCR kit was used for both tissue\/cytology samples and plasma samples.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EASSESS\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEGFR\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEuropean Continental Ancestry Group\/genetics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EAsian Continental Ancestry Group\/genetics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elung neoplasms\/genetics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elung neoplasms\/drug therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehuman EGFR protein\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EctDNA\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Enon\u2013small cell lung cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENSCLC\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT01785888\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoncology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ECirculating tumor DNA (ctDNA) was found to have utility for \u003Cem\u003EEGFR\u003C\/em\u003E mutation testing in advanced non\u2013small cell lung cancer (NSCLC) in a real-world setting in the diagnostic ASSESS study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01785888\u0026amp;atom=%2Fspmdc%2F15%2F8%2F7.atom\u0022\u003ENCT01785888\u003C\/a\u003E], according to Martin Reck, MD, PhD, Lung Clinic Grosshansdorf, Grosshansdorf, Germany.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe study enrolled 1288 eligible patients, with 997 from Europe and 291 from Japan. Overall, 75.8% of the patients were white and 23.0% were Asian; 19.6% were never-smokers; smokers had 40.0 median pack-years; and the majority of patients (84.6%) had stage IV disease.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe majority of the tissue\/cytology samples were obtained during the current diagnosis, derived from the primary tumor, and collected via bronchoscopy. Most samples were prepared as paraffin-embedded tissue blocks and fixed with 4% neutral-buffered formalin. The median turnaround time for \u003Cem\u003EEGFR\u003C\/em\u003E mutation testing was 11 days in Europe (95% CI, 14.0 to 17.3) and 8 days in Japan (95% CI, 8.2 to 14.1). The average test success rate was 98.3% in Europe and 99.6% in Japan.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EIn Japan, the tests used to evaluate tissue\/cytology samples and plasma samples for \u003Cem\u003EEGFR\u003C\/em\u003E mutations were Cycleave PCR and PNA LNA clamp PCR. In Europe, for tissue\/cytology testing, PNA LNA clamp PCR and the older methods of DNA sequencing and pyrosequencing were used, along with newer, more sensitive methods, including the Roche cobas \u003Cem\u003EEGFR\u003C\/em\u003E Mutation Test and Sequenom; for plasma testing, the QIAGEN Therascreen RGQ PCR kit and Roche cobas \u003Cem\u003EEGFR\u003C\/em\u003E Mutation Test were used.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe overall concordance was 89.1% (1035 of 1162 patients; 95% CI, 87.1 to 90.8) and overall positive predictive value (PPV) was 77.7% (87 of 112; 95% CI, 68.8 to 85.0). In patients in whom the same testing method was used for tissue\/cytology and plasma evaluations, the PPV was 92.6% (95% CI, 75.7 to 99.1) compared with 72.9% (95% CI, 62.2 to 82.0) when different testing methods were used for the evaluations. The sensitivity was 46.0% (95% CI, 38.8 to 53.4), specificity was 97.4% (95% CI, 96.2 to 98.3), and the negative predictive value was 90.3% (95% CI, 88.3 to 92.0) in the overall cohort.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe QIAGEN Therascreen RGQ PCR kit had a sensitivity of 72.7%, specificity of 99.1%, and PPV of 94.1% in this trial. A previous trial of white patients, IFUM [Douillard JY et al. \u003Cem\u003EBr J Cancer.\u003C\/em\u003E 2014], used the same kit and reported a sensitivity of 65.7%, specificity of 99.8%, and PPV of 98.6%.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EFalse-positive results, meaning an \u003Cem\u003EEGFR\u003C\/em\u003E mutation-positive plasma sample and an \u003Cem\u003EEGFR\u003C\/em\u003E mutation-negative tissue\/cytology sample, were believed to have come from 25 patients. These patients were from multiple sites and countries, indicating no specific laboratory-based issues. Among these patients, 56% of the tumors were tested by DNA sequencing or pyrosequencing (vs 25% of the overall population), 76% of the patients were never-, former-, or light-smokers (vs 45% of the overall population), and 32% of the tumor samples were needle biopsies\/cytology (vs 21% of the overall population). The false-positive rate may have been contributed to by possible over-representation of cytology samples, meaning inadequate tumor samples, or by use of the less sensitive DNA sequencing or pyrosequencing methodologies that had inadequate mutation analysis to detect mutation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EAmong the 191 patients overall who were \u003Cem\u003EEGFR\u003C\/em\u003E mutation positive, 30.6% of Japanese patients (86 of 281) and 11.6% of European patients (105 of 903) were positive. The exon 19 deletion was found in 51.3% (n\u2005=\u200540) of Japanese patients and in 54.5% (n\u2005=\u200554) of European patients. The L858R mutation only was found in 47.4% (n\u2005=\u200537) of Japanese patients and 28.3% (n\u2005=\u200528) of European patients. \u003Cem\u003EEGFR\u003C\/em\u003E mutation-positive status was significantly correlated with female sex, ADC histology, never-smoking status, and Japanese ethnicity (all \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001).\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003E\n            \u003Cem\u003EEGFR\u003C\/em\u003E mutation status was the largest driver of therapy choice. The most common first-line treatment decisions for all \u003Cem\u003EEGFR\u003C\/em\u003E mutation-positive patients were gefitinib, erlotinib, and afatinib; \u003Cem\u003EEGFR\u003C\/em\u003E mutation-negative patients most commonly received pemetrexed, radiation therapy, carboplatin, and cisplatin.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EAlthough practices for both tissue\/cytology and plasma samples require improvements, these real-world data from the large, observational ASSESS study suggest that ctDNA may be feasible and suitable for analyzing \u003Cem\u003EEGFR\u003C\/em\u003E mutations. The overall concordance of \u003Cem\u003EEGFR\u003C\/em\u003E mutation status was 89%.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/8\/7.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlnbf\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}